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Objectives: We identified functional genes and studied the underlying molecular mechanisms of diabetic cardiomyopathy (DCM) using bioinformatics tools., Methods: Original gene expression profiles were obtained from the GSE21610 and GSE112556 data sets. We used GEO2R to screen the differentially expressed genes (DEGs). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed on DEGs. Protein-protein interaction (PPI) networks of DEGs were constructed using STRING and hub genes of signaling pathways were identified using Cytoscape. Aberrant hub gene expression was verified using The Cancer Genome Atlas data set., Results: The DEGs in DCM were mainly enriched in the nuclei and cytoplasm and involved in DCM and chemokine-related signaling pathways. In the PPI network, 32 nodes were chosen as hub nodes and an RNA interaction network was constructed with 517 interactions. The expression of key genes (JPIK3R1, CCR9, XIST, WDFY3.AS2, hsa-miR-144-5p, and hsa-miR-146b-5p) was significantly different between DCM and normal tissues., Conclusions: The identified hub genes could be associated with DCM pathogenesis and could be used for treating DCM., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Glucose-regulated protein 75 (GRP75), a member of the heat-shock protein 70 family, is known to protect cells from stress-induced injury. However, information regarding its distribution and possible function in the retina is limited. In this study, we performed an optic nerve crush (ONC) model in adult rats and found that GRP75 was significantly upregulated in the retina after ONC. Double immunofluorescent staining revealed that GRP75 was localized in the retinal ganglion cells (RGCs). We also examined the expression profile of active caspase3, whose change was correlated with the expression profile of GRP75. In addition, we utilized co-staining of GRP75 and active caspase3 and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) to study their correlation in the retina following ONC. Furthermore, the expressions of Bax, cytochrome c (Cytc), p-extracellular-signal-regulated kinases (ERK)1/2, and p-AKT were enhanced in the retina after ONC, and they were parallel with the expression profile of GRP75. Based on our data, we speculated that GRP75 might play an important role in RGCs apoptosis following ONC.

CB1 and CB2 are multifunctional cannabinoid-specific receptors considered to be involved in inhibition of tumor development. To elucidate their roles in hepatocarcinogenesis, we analyzed the expression of these receptors in tumor and matched nontumorous tissues of human hepatocellular carcinoma (HCC) samples. In situ hybridization analysis showed overexpression of CB1 mRNAs in 8 of 13 (62%) HCC samples, and of CB2 mRNAs in 7 of 13 (54%). Immunohistochemical analysis of 64 HCC samples showed the expression of CB1 and CB2 receptors to increase from normal liver to chronic hepatitis to cirrhosis. Marked expression of CB1 and CB2 receptors was noted in the majority of cirrhotic liver samples (86 and 78%, respectively). In HCC, high expression of CB1 and CB2 receptors was observed in 29 (45%) and 33 (52%) cases, respectively. Clinicopathological evaluation indicated a significant correlation between CB1 and CB2 expression and two clinicopathological parameters such as the histopathological differentiation (P = 0.021 and 0.001, respectively), portal vein invasion (P = 0.015 and 0.004, respectively). Univariate analysis indicated that disease-free survival was significantly better in HCC patients with high versus those with low CB1 and CB2 expression levels (P = 0.010 and 0.037, respectively). Our results indicate that CB1 and CB2 have potential as prognostic indicators and suggest possible beneficial effects of cannabinoids on prognosis of patients with HCC.